MicroRNAs (miRNAs) in body fluids are candidate diagnostics for a variety of conditions and diseases, including breast cancer. One premise for using extracellular miRNAs to diagnose disease is the ...notion that the abundance of the miRNAs in body fluids reflects their abundance in the abnormal cells causing the disease. As a result, the search for such diagnostics in body fluids has focused on miRNAs that are abundant in the cells of origin. Here we report that released miRNAs do not necessarily reflect the abundance of miRNA in the cell of origin. We find that release of miRNAs from cells into blood, milk and ductal fluids is selective and that the selection of released miRNAs may correlate with malignancy. In particular, the bulk of miR-451 and miR-1246 produced by malignant mammary epithelial cells was released, but the majority of these miRNAs produced by non-malignant mammary epithelial cells was retained. Our findings suggest the existence of a cellular selection mechanism for miRNA release and indicate that the extracellular and cellular miRNA profiles differ. This selective release of miRNAs is an important consideration for the identification of circulating miRNAs as biomarkers of disease.
Cytokines of the interleukin-1 (IL-1) family, such as IL-1α/β and IL-18, have pleiotropic activities in innate and adaptive immune responses in host defense and diseases. Insight into their ...biological functions helped develop novel therapeutic approaches to treat human inflammatory diseases. IL-33 is an important member of the IL-1 family of cytokines and is a ligand of the ST2 receptor, a member of the IL-1 receptor family. However, the role of the IL-33/ST2 axis in tumor growth and metastasis of breast cancer remains unclear. Here, we demonstrate that IL-33 is a critical tumor promoter during epithelial cell proliferation and tumorigenesis in the breast. IL-33 dose- and time-dependently increased Cancer Osaka Thyroid (COT) phosphorylation via ST2-COT interaction in normal epithelial and breast cancer cells. The IL-33/ST2/COT cascade induced the activation of the MEK-ERK (MEK-extracellular signal-regulated kinase), JNK-cJun (cJun N-terminal kinase-cJun) and STAT3 (signal transducer and activator of transcription 3) signaling pathways, followed by increased AP-1 and stat3 transcriptional activity. When small interfering RNAs of ST2 and COT were introduced into cells, IL-33-induced AP-1 and stat3 activity were significantly decreased, unlike that in the control cells. The inhibition of COT activity resulted in decreased IL-33-induced epithelial cell transformation, and knockdown of IL-33, ST2 and COT in breast cancer cells attenuated tumorigenicity of breast cancer cells. Consistent with these observations, ST2 levels were positively correlated with COT expression in human breast cancer. These findings provide a novel perspective on the role of the IL-33/ST2/COT signaling pathway in supporting cancer-associated inflammation in the tumor microenvironment. Therapeutic approaches that target this pathway may, therefore, effectively inhibit carcinogenesis in the breast.
Aims/hypothesis
Obesity and insulin resistance are associated with low-grade chronic inflammation. Glucagon-like peptide-1 (GLP-1) is known to reduce insulin resistance. We investigated whether GLP-1 ...has anti-inflammatory effects on adipose tissue, including adipocytes and adipose tissue macrophages (ATM).
Methods
We administered a recombinant adenovirus (rAd) producing GLP-1 (rAd-GLP-1) to an
ob/ob
mouse model of diabetes. We examined insulin sensitivity, body fat mass, the infiltration of ATM and metabolic profiles. We analysed the mRNA expression of inflammatory cytokines, lipogenic genes, and M1 and M2 macrophage-specific genes in adipose tissue by real-time quantitative PCR. We also examined the activation of nuclear factor κB (NF-κB), extracellular signal-regulated kinase 1/2 and Jun N-terminal kinase (JNK) in vivo and in vitro.
Results
Fat mass, adipocyte size and mRNA expression of lipogenic genes were significantly reduced in adipose tissue of rAd-GLP-1-treated
ob/ob
mice. Macrophage populations (F4/80
+
and F4/80
+
CD11b
+
CD11c
+
cells), as well as the expression and production of IL-6, TNF-α and monocyte chemoattractant protein-1, were significantly reduced in adipose tissue of rAd-GLP-1-treated
ob/ob
mice. Expression of M1-specific mRNAs was significantly reduced, but that of M2-specific mRNAs was unchanged in rAd-GLP-1-treated
ob/ob
mice. NF-κB and JNK activation was significantly reduced in adipose tissue of rAd-GLP-1-treated
ob/ob
mice. Lipopolysaccharide-induced inflammation was reduced by the GLP-1 receptor agonist, exendin-4, in 3T3-L1 adipocytes and ATM.
Conclusions/interpretation
We suggest that GLP-1 reduces macrophage infiltration and directly inhibits inflammatory pathways in adipocytes and ATM, possibly contributing to the improvement of insulin sensitivity.
ABSTRACT We present ground-based optical photometric monitoring data for NGC 5548, part of an extended multiwavelength reverberation mapping campaign. The light curves have nearly daily cadence from ...2014 January to July in nine filters (BVRI and ugriz). Combined with ultraviolet data from the Hubble Space Telescope and Swift, we confirm significant time delays between the continuum bands as a function of wavelength, extending the wavelength coverage from 1158 Å to the z band (~9160 Å). We find that the lags at wavelengths longer than the V band are equal to or greater than the lags of high-ionization-state emission lines (such as He ii λ 1640 and λ 4686 ), suggesting that the continuum-emitting source is of a physical size comparable to the inner broad-line region (BLR). The trend of lag with wavelength is broadly consistent with the prediction for continuum reprocessing by an accretion disk with τ ∝ λ 4 / 3 . However, the lags also imply a disk radius that is 3 times larger than the prediction from standard thin-disk theory, assuming that the bolometric luminosity is 10% of the Eddington luminosity ( L = 0.1 L Edd ). Using optical spectra from the Large Binocular Telescope, we estimate the bias of the interband continuum lags due to BLR emission observed in the filters. We find that the bias for filters with high levels of BLR contamination (~20%) can be important for the shortest continuum lags and likely has a significant impact on the u and U bands owing to Balmer continuum emission.
Total number concentrations of particles having a diameter larger than 10 nm (NCN), cloud condensation nuclei at several supersaturation (S) values (NCCN) and number size distributions of particles ...with 10–414 nm diameter were measured in Seoul between 2004 and 2010. Overall average values of NCN and geometric mean diameter were 17 811 ± 5581 cm−3 and 48 ± 6 nm. Average NCCN at 0.4, 0.6 and 0.8% S were 4145 ± 2016, 5323 ± 2453 and 6067 ± 2780 cm−3 and corresponding NCCN / NCN were 0.26 ± 0.11, 0.33 ± 0.11 and 0.37 ± 0.12. There is a clear seasonal variation in aerosol concentration, which seems to be due to the monsoon. NCN and NCCN are also found to depend on the volume of traffic and the height of the planetary boundary layer, respectively. During aircraft campaigns in 2009 and 2011, NCN and NCCN at 0.6% S (N0.6%) were measured in and around the Korean Peninsula. During the 2011 campaign, the aerosol scattering coefficient was also measured. NCN and N0.6% in the lower altitudes were generally higher than at higher altitudes, except for cases when particle formation and growth events were thought to occur at higher altitudes. NCN and N0.6% generally show a positive correlation with aerosol scattering coefficients but this correspondence tends to vary with altitude. Occasional instances of low (< 0.3) N0.6% / NCN in the boundary layer are demonstrated to be associated with particle formation and growth events. With the support of ground measurements, it is confirmed that a particle formation and growth event did indeed occur over the Yellow Sea on a flight day, and the areal extent of this event is estimated to be greater than 100 km × 450 km. With the combination of the current and several relevant previous studies, a composite map of NCN and NCCN in and around the Korean Peninsula is produced. Overall, the exhibited concentrations are typical of values measured over polluted regions elsewhere on the globe. Moreover, there is a generally decreasing trend from west to east over the region, implying that the region is constantly under the dominant influence of continental outflow.
Decays of heavy pseudoscalar mesons B, Bc, Bs, and Ds at the LHCb upgrade are considered, which produce either two equal sign muons or taus. In addition, we consider the analogous decays with ...opposite sign muons or taus. All these decays are considered to be mediated by a heavy on-shell neutrino N. Such decays of B mesons, if not detected, will give, in general, stringent upper bounds on the heavy-light mixing parameter |UμN|2 as a function of the neutrino mass MN ~ 1 GeV, principally due to the large expected number of produced mesons B. While some of the decays of the other mentioned mesons are attractive due to a weaker Cabibbo-Kobayashi-Maskawa suppression, the expected produced number of such mesons is significantly smaller that of B's; therefore, the sensitivity bounds from such decays are, in general, comparable or less restrictive. When τ pairs are produced, only two types of such decays are significant: B±, Bc± → τ±τ±π∓ (and τ±τ∓π±), giving us stringent upper bounds on |UτN|2; the other decays with a pair of τ, such as B0 → D(*)−τ+τ+π− (and D(*)−τ+τ−π+), are prohibited or very suppressed by kinematics.
Alpha backgrounds in the AMoRE-Pilot experiment Alenkov, V.; Bae, H. W.; Beyer, J. ...
The European physical journal. C, Particles and fields,
12/2022, Letnik:
82, Številka:
12
Journal Article
Recenzirano
Odprti dostop
The Advanced Mo-based Rare process Experiment (AMoRE)-Pilot experiment is an initial phase of the AMoRE search for neutrinoless double beta decay of
100
Mo, with the purpose of investigating the ...level and sources of backgrounds. Searches for neutrinoless double beta decay generally require ultimately low backgrounds. Surface
α
decays on the crystals themselves or nearby materials can deposit a continuum of energies that can be as high as the
Q
-value of the decay itself and may fall in the region of interest (ROI). To understand these background events, we studied backgrounds from radioactive contaminations internal to and on the surface of the crystals or nearby materials with Geant4-based Monte Carlo simulations. In this study, we report on the measured
α
energy spectra fitted with the corresponding simulated spectra for six crystal detectors, where sources of background contributions could be identified through high energy
α
peaks and continuum parts in the energy spectrum for both internal and surface contaminations. We determine the low-energy contributions from internal and surface
α
contaminations by extrapolating from the
α
background fitting model.
In view of the projected high number of produced B mesons in the Belle II experiment (∼1010 per year), in addition to the ongoing LHC-b, we calculate the rate of decay for the rare decays of B mesons ...via a sterile on-shell neutrino N, which subsequently may decay leptonically or semileptonically within the detector: B→(D(*))ℓ1±N, then N→ℓ1±ℓ2∓ν or N→ℓ±π∓. Here, ℓ1≠ℓ2 in order to avoid serious QED background. We account for the possible effects of the neutrino lifetime on the observability of the rare decays. If no charmed mesons D(*) are produced at the first vertex of the sterile neutrino, a strong Cabibbo-Kobayashi-Maskawa (CKM) suppression becomes effective; this is not true if we consider instead the decays of Bc mesons, which can be produced copiously in LHC-b. The production of charmed mesons D(*) at the first vertex offers an attractive possibility because it avoids strong CKM suppression. Such rare decays of B mesons could be detected at the Belle II experiment, with the N neutrino either decaying within the detector or manifesting itself as a massive missing momentum.
Sweet potato leaf curl virus (SPLCV) infects sweet potato and is a member of the family Geminiviridae (genus Begomovirus). SPLCV transmission occurs from plant to plant mostly via vegetative ...propagation as well as by the insect vector Bemisia tabaci. When sweet potato seeds were planted and cultivated in a whitefly‐free greenhouse, some sweet potato plants started to show SPLCV‐specific symptoms. SPLCV was detected by PCR from all leaves and floral tissues that showed leaf curl disease symptoms. More than 70% of the seeds harvested from SPLCV‐infected sweet potato plants tested positive for SPLCV. SPLCV was also identified from dissected endosperm and embryos. The transmission level of SPLCV from seeds to seedlings was up to 15%. Southern blot hybridization showed SPLCV‐specific single‐ and double‐stranded DNAs in seedlings germinated from SPLCV‐infected seeds. Taken altogether, the results show that SPLCV in plants of the tested sweet potato cultivars can be transmitted via seeds and SPLCV DNA can replicate in developing seedlings. This is the first seed transmission report of SPLCV in sweet potato plants and also, to the authors' knowledge, the first report of seed transmission for any geminivirus.
We study the purely leptonic decays of W super(+ or -)arrowrighte super(+ or -)e super(+ or -)mu super(?)nu and mu super(+ or -)mu super(+ or -)e super(?)nu produced at the LHC, induced by sterile ...neutrinos with mass m sub(N) below M sub(W) in the intermediate state. Since the final state neutrino escapes detection, one cannot tell whether this process violates lepton number, which would indicate a Majorana character for the intermediate sterile neutrino. Our study shows that when the sterile neutrino mixings with electrons and muons are different enough, one can still discriminate between the Dirac and Majorana character of this intermediate neutrino by simply counting and comparing the above decay rates. After performing collider simulations and statistical analysis, we find that at the 14 TeV LHC with an integrated luminosity of 3000fb super(?1), for two benchmark scenarios m sub(N)=20 and 50 GeV, at least a 3sigma level of exclusion on the Dirac case can be achieved for disparities as mild as, e.g., U sub(Ne) super(2)<0.7U sub(Nmu) super(2) or U sub(N)mu super(2)<0.7U sub(Ne) super(2), provided that U sub(N)u2and U sub(N)mu super(2) are both above ~2x10 super(?6).
PDF
